GFR alpha -1, -2, -3, and -4 are GPI-anchored receptors that interact preferentially with the GDNF family ligands GDNF, Neurturin, Artemin, and Persephin, respectively. GFR alpha proteins initiate signaling in association with the receptor tyrosine kinase RET and by RET-independent pathways. GFR alpha-mediated signaling is instrumental in the differentiation, migration, and support of central and peripheral neurons. Alternative splicing generates multiple isoforms of GFR alpha proteins.